The invention herein is directed to a process for preparing prostaglandin analogs which can be performed in a single reaction vessel, in high yields and in the proper stereoconfiguration for the prostaglandin analogs. The invention herein is further directed to a process for preparing higher order cuprate complexes of the general formula ##STR1## from alkenyl zirconium compounds as reactive intermediates in organic synthesis. The higher order cuprate complexes are derived from the reaction of a cuprate complex with an alkenyl zirconium compound. The higher order cuprate complexes are useful for preparing omega side chains of prostaglandin analogs and more specifically, 16-hydroxy prostaglandin analog side chains.
The state of the art of higher order cuprate complexes is summarized in Synthesis, 4, p. 325, (1987) where higher order cuprate complexes of the formulae R.sub.t RCu(CN)Li.sub.2, R.sub.t Cu(2-thienyl)CNLi.sub.2, and R.sub.t RCu(SCN)Li.sub.2 and their uses are disclosed. R.sub.t represents the group transferred to an organic compound to form a carbon to carbon bond in a subsequent reaction with the disclosed higher order cuprate complex.
The use of zirconium compounds to prepare prostaglandins is shown in published European patent application 153,689 which describes the preparation of prostaglandin intermediates. The application describes a zirconium compound of the formula ##STR2## wherein X is a halogen and P.sup.1 represents a hydrolyzable protecting group. The zirconium compound is reacted with a compound having the formula ##STR3## wherein CO.sub.2 P.sup.2 represents a hydrolyzable ester group, in an anhydrous, inert organic solvent which contains a salt or a complex of a transition metal as a catalyst. The reaction mixture is treated with a protonating agent to produce a prostaglandin analog compound of the formula ##STR4## The reference describes the use of the zirconium compounds to add an unsaturated omega side chain on a cyclopentenone to form a prostaglandin analog. The reference discloses that the reaction occurs in the presence of a salt or a complex of a transition metal catalyst which includes salts or complexes of nickel, cobalt, iron, manganese and palladium. The reference's preferred complex is a complex or salt of nickel (I) which is produced in situ in the reaction by using a nickel (II) salt (or complex) and a reducing agent.